Lipid peroxidation causes endosomal antigen release for cross-presentation.
Lipid peroxidation causes endosomal antigen release for cross-presentation.
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DOI：
10.1038/srep22064
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发表时间：
2016-02-24
影响因子：
4.6
通讯作者：
van den Bogaart G
中科院分区：
文献类型：
--
作者：
Dingjan I;Verboogen DR;Paardekooper LM;Revelo NH;Sittig SP;Visser LJ;Mollard GF;Henriet SS;Figdor CG;Ter Beest M;van den Bogaart G
树突状细胞（Dendritic cells，DCs）通过交叉呈递（cross-presentation）的方式将外源性抗原以主要组织相容性复合体（major histocompatibility complex，MHC）I类分子的形式呈递给细胞毒性T细胞。在这一过程中的一个重要步骤是抗原从内体腔释放到胞质溶胶中，但这一步骤的机制仍不清楚。在这项研究中，我们表明，活性氧（ROS）产生的NADPH氧化酶复合物NOX 2引起脂质过氧化，膜破坏链反应，这反过来又导致抗原泄漏内体。通过阻断ROS产生或清除自由基来抑制抗原渗漏和交叉呈递，并且当使用ROS生成光敏剂时诱导。来自NOX 2功能障碍的慢性肉芽肿病（CGD）患者的DC中内体抗原释放受损。因此，N 0X 2通过直接氧化内体脂质诱导抗原从内体释放用于交叉呈递。这构成了ROS在调节针对病原体和癌症的免疫应答中的新的细胞功能。
Dendritic cells (DCs) present foreign antigen in major histocompatibility complex (MHC) class I molecules to cytotoxic T cells in a process called cross-presentation. An important step in this process is the release of antigen from the lumen of endosomes into the cytosol, but the mechanism of this step is still unclear. In this study, we show that reactive oxygen species (ROS) produced by the NADPH-oxidase complex NOX2 cause lipid peroxidation, a membrane disrupting chain-reaction, which in turn results in antigen leakage from endosomes. Antigen leakage and cross-presentation were inhibited by blocking ROS production or scavenging radicals and induced when using a ROS-generating photosensitizer. Endosomal antigen release was impaired in DCs from chronic granulomatous disease (CGD) patients with dysfunctional NOX2. Thus, NOX2 induces antigen release from endosomes for cross-presentation by direct oxidation of endosomal lipids. This constitutes a new cellular function for ROS in regulating immune responses against pathogens and cancer.